2-Pyridone

vanc changed 477215516 2-Pyridone 2-pyridone.svg 2-pyridone_(lactam).svg 150px 2-Pyridone 150px 2-Pyridone-(lactam)-3D-balls.png 2-Pyridone molecule (lactam form) 2-Pyridone-(lactim)-3D-balls.png 2-Pyridone molecule (lactim form) Pyridin-2(1H)-oneInternational Union of Pure and Applied Chemistry 2014 Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 https://iupac.qmul.ac.uk/BlueBook/ The Royal Society of Chemistry P-44.4.1.8 10.1039/9781849733069 978-0-85404-182-4 2(1H)-Pyridinone2(1H)-Pyridone1H-Pyridine-2-one2-Pyridone1,2-Dihydro-2-oxopyridine1H-2-Pyridone2-Oxopyridone2-Pyridinol2-Hydroxypyridine correct EBI 16540 Oc1ccccn1 lactim correct chemspider 8537 1/C5H5NO/c7-5-2-1-3-6-4-5/h1-4,7H GRFNBEZIAWKNCO-UHFFFAOYAT 1/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7) UBQKCCHYAOITMY-UHFFFAOYAK C1=CC=CNC(=O)1 lactam correct EBI 662 correct chemspider 1S/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7) correct chemspider UBQKCCHYAOITMY-UHFFFAOYSA-N correct CAS 142-08-5 correct FDA 6770O3A2I5 UV1144050 205-520-3 8871 C02502 5 5 1 1 Colourless crystalline solid 1.39 g/cm3 other solvents Soluble in water,methanol, acetone 107.8 280 decomp. 11.65 293 nm (ε 5900, H2O soln) planar Orthorhombic 4.26 D irritating 2 1 210 06 07 Danger 301 315 319 335 261 264 270 271 280 301+310 302+352 304+340 305+351+338 312 321 330 332+313 337+313 362 403+233 405 501 2-Pyridinolate 2-Hydroxypyridinium-ion functional groups alcohol, lactam, lactim,pyridine, ketone pyridine, thymine, cytosine,uracil, benzene 2-Pyridone is an organic compound with the formula C 5 H 4 NH(O). It is a colourless solid. It is well known to form hydrogen bonded dimers and it is also a classic case of a compound that exists as tautomers. Tautomerism and aggregation Pyridone is tautomeric with 2-hydroxypyridine: 180px|tautomerism|centerSimilar lactam-lactim tautomerism can also be exhibited in many related compounds.Forlani L. Cristoni G. Boga C. Todesco P. E. Del Vecchio E. Selva S. Monari M. Reinvestigation of tautomerism of some substituted 2-hydroxypyridines Arkivoc 2002 198–215 XI 11 10.3998/ark.5550190.0003.b18 free 2027/spo.5550190.0003.b18 free The tautomerization has been exhaustively studied. The energy difference appears to be very small, and the dominant tautomer depends strongly on the phase of matter. The energy difference in the gas phase was measured by IR spectroscopy to be 2.43 to 3.3 kJ/mol for the solid state and 8.83 to 8.95 kJ/mol for the liquid state.Brown R. S. Tse A. Vederas J. C. Photoelectro-Determined Core Binding Energies and Predicted Gas-Phase Basicities for the 2-Hydroxypyridine 2-Pyridone System Journal of the American Chemical Society 1980 1174–1176 3 10.1021/ja00523a050 102 Beak P. Energies and Alkylation of Tautomeric Heterocyclic-Compounds - Old Problems New Answers Acc. Chem. Res. 1977 186–192 5 10.1021/ar50113a006 10Abdulla H. I. El-Bermani M. F. Infrared studies of tautomerism in 2-hydroxypyridine 2-thiopyridine and 2-aminopyridine Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2001 2659–2671 13 10.1016/S1386-1425(01)00455-3 11765793 57 2001AcSpA..57.2659A The predominant solid state form is 2-pyridone, as confirmed by X-ray crystallographyYang H. W. Craven B. M. Charge Density of 2-Pyridone Acta Crystallogr. B 1998 912–920 10.1107/S0108768198006545 54 9880899 6 9505447 Penfold B. R. The Electron Distribution in Crystalline Alpha Pyridone Acta Crystallogr. 1953 591–600 6 10.1107/S0365110X5300168X 7 free 1953AcCry...6..591P Ohms U. Guth H. Heller E. Dannöhl H. Schweig A. Comparison of Observed and Calculated Electron-Density 2-Pyridone, C5H5NO, Crystal-Structure Refinements at 295K and 120K, Experimental and Theoretical Deformation Density Studies Z. Kristallogr. 1984 185–200 169 10.1524/zkri.1984.169.14.185 97575334 Almlöf J. Kvick A. Olovsson I. Hydrogen Bond Studies Crystal Structure of Intermolecular Complex 2-Pyridone-6-Chloro-2-Hdroxypyridine Acta Crystallogr. B 1971 1201–1208 10.1107/S0567740871003753 27 6 and IR spectroscopy.August 2026 Non-polar solvents generally favour 2-hydroxypyridine whereas polar solvents such as alcohols and water favour the 2-pyridone.Aue DH, Betowski LD, Davidson WR, Bower MT, Beak P Gas-Phase Basicities of Amides and Imidates - Estimation of Protomeric Equilibrium-Constantes by the Basicity methode in the Gas-Phase Journal of the American Chemical Society 1979 1361–1368 6 10.1021/ja00500a001 101 1979JAChS.101.1361A Frank J., Alan R. Katritzky Tautomeric pyridines. XV. Pyridone-hydroxypyridine equilibria in solvents of different polarity J Chem Soc Perkin Trans 2 1976 1428–1431 10.1039/p29760001428 12 In either case, the amide group can be involved in hydrogen bonding. 2-Pyridone, 2-hydroxypyridine, and substituted derivatives can form dimers with two hydrogen bonds...Hammes GG, Lillford PJ A Kinetic and Equilibrium Study of Hydrogen Bond Dimerization of 2-Pyridone in Hydrogen Bonding Solvent J. Am. Chem. Soc. 1970 7578–7585 26 10.1021/ja00729a012 92 alt=dimer|center|200x200px ...but X-ray crystallography indicates that the parent compounds do not so dimerize in the solid state; instead, the 2-pyridones form a helical structure. Contrariwise, some substituted 2-pyridones, for example 5-methyl-3-carbonitrile-2-pyridone, adopt solid-state dimers. In solution the dimeric form is present; the ratio of dimerisation is strongly dependent on the polarity of the solvent. Polar and protic solvents can hydrogen-bond directly to pyridone, and the equilibrium shifts towards the monomer. Hydrophobic effects in non-polar solvents lead to a predominance of the dimer. In any given system, all possible tautomers and dimers can be present and form an equilibrium, and the exact measurement of all the equilibrium constants is extremely difficult. Tautomeric transition is generally believed to occur through multimolecular pathways. A monomolecular mechanism would require a forbidden 1-3 suprafacial transition state, and theoretical methods compute an energy barrier between 125 and 210 kJ/mol. Dimerisation, followed by double proton transfer and dissociation, is an autocatalytic path from one tautomer to the other. Protic solvents also mediate proton transfer during tautomerisation. Synthesis 2-Pyrone can be obtained by a cyclisation reaction, and converted to 2-pyridone via an exchange reaction with ammonia: 350px|2-Pyridone synthesis from 2-pyran Pyridine forms an N-oxide with some oxidation agents such as hydrogen peroxide. This pyridine-N-oxide undergoes a rearrangement reaction to 2-pyridone in acetic anhydride:Pyridin-N-oxydと酸無水物との反應 Reaction between Pyridin-N-oxyd and acid anhydride 10.1248/yakushi1947.67.3-4_51 ja 1947 Yakugaku Zasshi 67 3–4 51–52 free10.1021/jo01133a010 Recent Japanese Work on the Chemistry of Pyridine 1-Oxide and Related Compounds The Journal of Organic Chemistry 18 5 534–551 1953 Ochiai Eiji.10.1021/jo01061a037 The Rearrangement of Substituted Pyridine N-Oxides with Acetic Anhydride1.2 The Journal of Organic Chemistry 26 2 428–430 1961 Boekelheide V. Lehn W. L. 250px|2-Pyridone synthesis from pyridine-N-oxide In the Guareschi-Thorpe condensation cyanoacetamide reacts with a 1,3-diketone to a 2-pyridone.Gilchrist, T.L. (1997). Heterocyclic Chemistry 0-470-20481-8Rybakov V. R. Bush A. A. Babaev E. B. Aslanov L. A. 3-Cyano-4,6-dimethyl-2-pyridone (Guareschi Pyridone) Acta Crystallogr E 2004 o160–o161 6 10.1107/S1600536803029295 2 2004AcCrE..60O.160R The reaction is named after Icilio Guareschi and Jocelyn Field Thorpe. I. Guareschi Mem. Reale Accad. Sci. Torino II 1896Baron, H. Remfry, F. G. P. Thorpe, J. F. CLXXV.-The formation and reactions of imino-compounds. Part I. Condensation of ethyl cyanoacetate with its sodium derivative J. Chem. Soc., Trans. 85 1726–1761 1904 10.1039/ct9048501726 https://zenodo.org/record/1429705 2020-06-05 2020-09-14 https://web.archive.org/web/20200914183246/https://zenodo.org/record/1429705 live Chemical properties Catalytic activity 2-Pyridone catalyses a variety of proton-dependent reactions, for example the aminolysis of esters. In some cases, molten 2-pyridone is used as a solvent. 2-Pyridone has a large effect on the reaction from activated esters with amines in nonpolar solvent, which is attributed to its tautomerisation and utility as a ditopic receptor. Proton transfer from 2-pyridone and its tautomer have been investigated by isotope labeling, kinetics and quantum chemical methods.Fischer C. B. Steininger H. Stephenson D. S. Zipse H. Catalysis of Aminolysis of 4-Nitrophenyl Acetate by 2-Pyridone Journal of Physical Organic Chemistry 2005 901–907 18 9 10.1002/poc.914L.-H. Wang H. Zipse 1996 Bifunctional Catalysis of Ester Aminolysis - A Computational and Experimental Study Liebigs Ann. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/jlac.199619961003 1996 10 1501–1509 10.1002/jlac.199619961003 2021-09-01 2021-09-01 https://web.archive.org/web/20210901174459/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/jlac.199619961003 live subscriptionFischer C. B. Polborn K. Steininger H. Zipse H. Synthesis and Solid-State Structures of Alkyl-Substituted 3-Cyano-2-pyridones Zeitschrift für Naturforschung 59 2004 1121–1131 59b http://www.znaturforsch.com/sb/s59b1121.pdf subscription required 10.1515/znb-2004-1008 98273691 2006-11-07 2008-10-30 https://web.archive.org/web/20081030022754/http://www.znaturforsch.com/sb/s59b1121.pdf dead Coordination chemistry 2-Pyridone and some derivatives serve as ligands in coordination chemistry, usually as a 1,3-bridging ligand akin to carboxylate.Rawson J. M. Winpenny R. E. P. The coordination chemistry of 2-pyridones and its derivatives Coordination Chemistry Reviews 1995 313–374 139 10.1016/0010-8545(94)01117-T 139 In nature 2-Pyridone is not naturally occurring, but a derivative has been isolated as a cofactor in certain hydrogenases.Shima, S.; Lyon, E. J.; Sordel-Klippert, M.; Kauss, M.; Kahnt, J.; Thauer, R. K.; Steinbach, K.; Xie, X.; Verdier, L. and Griesinger, C., "Structure elucidation: The cofactor of the iron-sulfur cluster free hydrogenase Hmd: structure of the light-inactivation product", Angew. Chem. Int. Ed., 2004, 43, 2547-2551. Environmental behavior 2-Pyridone is rapidly degraded by microorganisms in the soil environment, with a half life less than one week. 10.2134/jeq1985.00472425001400040022x http://jeq.scijournals.org/cgi/content/abstract/14/4/580 580–584 Journal of Environmental Quality Degradation of Pyridine Derivatives in Soil 14 4 Sims, Gerald K. S 1985 1985JEnvQ..14..580S dead https://archive.today/20080830100452/http://jeq.scijournals.org/cgi/content/abstract/14/4/580 2008-08-30 subscription Organisms capable of growth on 2-pyridone as a sole source of carbon, nitrogen, and energy have been isolated by a number of researchers. The most extensively studied 2-pyridone degrader is the gram-positive bacterium Arthrobacter crystallopoietes, 10.1007/BF00422519 14106078 137–153 A crystalline pigment produced from 2-hydroxypyridine by arthrobacter crystallopoietes n.sp 1963 Ensign Jerald C. Rittenberg Sydney C. Archiv für Mikrobiologie 47 2 1963ArMic..47..137E 6389661 a member of the phylum actinomycetota. Numerous actinomycetotes have been shown to degrade pyridine or alkyl-, carboxyl-, or hydroxyl-substituted derivatives. 2-Pyridone degradation is commonly initiated by mono-oxygenase attack, resulting in a diol, such as 2,5-dihydroxypyridine, which is metabolized via the maleamate pathway. Fission of the ring proceeds via action of 2,5-dihydroxypyridine monooxygenase, which is also involved in metabolism of nicotinic acid via the maleamate pathway. In the case of Arthrobacter crystallopoietes, at least part of the degradative pathway is plasmid-borne. 10.1080/10643388909388372 http://www.mesg.anl.gov/Ed_web_files/oloughlinPDF_Files/CREC1989.pdf Sims G. K. E.J. O'Loughlin Crawford 1989 Ronald Degradation of pyridines in the environment CRC Critical Reviews in Environmental Control 19 4 309–340 1989CRvEC..19..309S dead https://web.archive.org/web/20100527212347/http://www.mesg.anl.gov/Ed_web_files/oloughlinPDF_Files/CREC1989.pdf 2010-05-27 Analytical data y NMR spectroscopy 290px|NMR data of 2-Pyridone 1H-NMR 1H-NMR (400 MHz, CD3OD): /ρ = 8.07 (dd,3J = 2.5 Hz,4J = 1.1 Hz, 1H, C-6), 7.98 (dd,3J = 4.0 Hz,3J = 2.0 Hz, 1H, C-3), 7.23 (dd,3J = 2.5 Hz,3J = 2.0 Hz, 1H, C-5), 7.21 (dd,3J = 4.0 Hz,4J = 1.0 Hz, 1H, C-4). 13C-NMR (100.57 MHz, CD3OD): ρ = 155.9 (C-2), 140.8 (C-4), 138.3 (C-6), 125.8 (C-3), 124.4 (C-5) UV/Vis spectroscopy (MeOH):νmax (lg ε) = 226.2 (0.44), 297.6 (0.30). IR spectroscopy (KBr): ν = 3440 cm−1–1 (br, m), 3119 (m), 3072 (m), 2986 (m), 1682 (s), 1649 (vs), 1609 (vs), 1578 (vs), 1540 (s), 1456 (m), 1433 (m), 1364 (w), 1243 (m), 1156 (m), 1098 (m), 983 (m), 926 (w), 781 (s), 730 (w), 612 (w), 560 (w), 554 (w), 526 (m), 476 (m), 451 (w). Mass spectrometry EI-MS (70 eV): m/z (%) = 95 (100) [M+], 67 (35) [M+ - CO], 51 (4)[C4H3+]. References Cox R. H. Bothner-By A. A. 10.1021/j100842a001 Proton magnetic resonance spectra of tautomeric substituted pyridines and their conjugate acids The Journal of Physical Chemistry 73 8 2465 1969 Substituent and solvent effects in the proton magnetic resonance (PMR) spectra of six 2-substituted pyridines DW Aksnes 1972 Acta Chemica Scandinavica 26 2255–2266 http://actachemscand.org/pdf/acta_vol_26_p2255-2266.pdf 10.3891/acta.chem.scand.26-2255 16 July 2025 6 March 2012 5 July 2024 https://web.archive.org/web/20120306211354/http://actachemscand.org/pdf/acta_vol_26_p2255-2266.pdf dead Brügel W. 1962 Die Kernresonanzspektren von Pyridin-Derivaten Zeitschrift für Elektrochemie, Berichte der Bunsengesellschaft für physikalische Chemie 66 2 159–177 10.1002/bbpc.19620660211 98754100 https://www.researchgate.net/publication/230372754 Roberts J. D. Von Ostwalden P. W. 10.1021/jo00823a029 Nuclear magnetic resonance specroscopy. Proton spectra of 2-pyridones The Journal of Organic Chemistry 36 24 3792 1971 See also 2-Pyrone 4-Pyridone The 5-methyl-2-pyridone is used to make pirfenidone. References 2 Further reading General Engdahl K. Ahlberg P. Journal of Chemical Research 1977 340–341 Bensaude O, Chevrier M, Dubois J Lactim-Lactam Tautomeric Equilibrium of 2-Hydroxypyridines. 1.Cation Binding, Dimerization and Interconversion Mechanism in Aprotic Solvents. A Spectroscopic and Temperature-Jump Kinetic Study J. Am. Chem. Soc. 1978 7055–7066 10.1021/ja00490a046 100 22 1978JAChS.100.7055B Bensaude O, Dreyfus G, Dodin G, Dubois J Intramolecular Nondissociative Proton Transfer in Aqueous Solutions of Tautomeric Heterocycles: a Temperature-Jump Kinetic Study J. Am. Chem. Soc. 1977 4438–4446 10.1021/ja00455a037 99 13 1977JAChS..99.4438B Bensaude O, Chevrier M, Dubois J Influence of Hydration upon Tautomeric Equilibrium Tetrahedron Lett. 1978 2221–2224 10.1016/S0040-4039(01)86850-7 19 25 Hammes GG, Park AC Kinetic and Thermodynamic Studies of Hydrogen Bonding J. Am. Chem. Soc. 1969 956–961 10.1021/ja01032a028 91 4 1969JAChS..91..956H Hammes GG, Spivey HO A Kinetic Study of the Hydrogen-Bond Dimerization of 2-Pyridone J. Am. Chem. Soc. 1966 1621–1625 10.1021/ja00960a006 8 88 5942979 1966JAChS..88.1621H Beak P, Covington JB, Smith SG Structural Studies of Tautomeric Systems: the Importance of Association for 2-Hydroxypyridine-2-Pyridone and 2-Mercaptopyridine-2-Thiopyridone J. Am. Chem. Soc. 1976 8284–8286 10.1021/ja00441a079 98 25 1976JAChS..98.8284B Beak P, Covington JB, White JM Quantitave Model of Solvent Effects on Hydroxypyridine-Pyridone and Mercaptopyridine-Thiopyridone Equilibria: Correlation with Reaction-Field and Hydrogen-Bond Effects J. Org. Chem. 1980 1347–1353 10.1021/jo01296a001 45 8 Beak P, Covington JB, Smith SG, White JM, Zeigler JM Displacement of Protomeric Equilibria by Self-Association: Hydroxypyridine-Pyridone and Mercaptopyridine-Thiopyridone Isomer Pairs J. Org. Chem. 1980 1354–1362 10.1021/jo01296a002 45 8 Tautomerism Vögeli U. von Philipsborn W. C-13 and H-1 NMR Spectroscopie Studies on Structure of N-Methyle-3-Pyridone and 3-Hydroypyridine Org Magn Reson 1973 551–559 10.1002/mrc.1270051202 5 12 Specker H. Gawrosch H. Ultraviolet absorption of benztriaxole, pryridone and its salts Chem. Ber. 1942 1338–1348 75 10.1002/cber.19420751115 Leis D. G. Curran B. C. Electric Moments of Some Gamma-Substituted Pyridines Journal of the American Chemical Society 1945 79–81 1 10.1021/ja01217a028 67 1945JAChS..67...79L Albert A. Phillips J. N. Ionisation Constants of Heterocyclic Substances Hydroxy-Derivates of Nitrogenous Six-Membered Ring-Compounds J. Chem. Soc. 1956 1294–1304 10.1039/jr9560001294 Cox R. H. Bothner-By A. A Proton Magnetic Resonance Spectra of Tautomeric Substituted Pyridines and Their Conjugated Acides J. Phys. Chem. 1969 2465–2468 8 10.1021/j100842a001 73 Aksnes DW, Kryvi Substituent and Solvent Effects in Proton Magnetic -Resonance (PMR) Spectra of 6 2-Substituted Pyridines Acta Chem. Scand. 1972 2255–2266 26 10.3891/acta.chem.scand.26-2255 26 Kryvi Håkon Samuelson Olof Sjöstrand Elisabeth Svensson Sigfrid 16 July 2025 free Category:Catalysts Category:Lactims